Moving Beyond Chemotherapy in Relapsed/Refractory ES-SCLC Treatment

Later lines of therapy in the treatment of extensive-stage small cell lung cancer (ES-SCLC) has been enhanced with tarlatamab-dlle (Imdelltra), a DLL3/CD3 T-cell engager.

In an interview with CancerNetwork®, Bingnan Zhang, MD, MBA, an assistant professor in the Department of Thoracic/Head and Neck Medical Oncology in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discussed standard treatment options for patients with ES-SCLC harboring brain metastases leading up to the FDA approval of the agent for the treatment of patients with ES-SCLC who experienced disease progression on or after platinum-based chemotherapy in May 2024.

Touching upon frontline options for ES-SCLC, Zhang suggested that a chemoimmunotherapy regimen with immunotherapy maintenance with either atezolizumab (Tecentriq) and durvalumab (Imfinzi) are standard for this setting. Beyond that, she explained that chemotherapy has been the standard for subsequent lines prior to the approval of the T-cell engager.

Specifically, topotecan was considered the standard-of-care second-line option for years before lurbinectedin (Zepzelca) was introduced in this setting. However, following the May 2024 approval, Zhang explained that tarlatamab is increasingly becoming the new standard for the treatment of relapsed ES-SCLC.

Transcript:

Standard of care for patients with extensive-stage small cell lung cancer, [who] are the majority of patients, about 70%, diagnosed with extensive-stage or with metastatic disease, has been a chemoimmunotherapy combination in the first-line treatment followed by immunotherapy maintenance. That’s our PD-L1 inhibitors, atezolizumab or durvalumab.

If the patient’s disease progresses after this initial treatment, then the previous standard-of-care has been different types of chemotherapy medications. Topotecan has been the only chemotherapy approved for many years, and in more recent years, lurbinectedin has also been used in these settings. Tarlatamab, which is a DLL3/CD3 T-cell engager, has recently demonstrated superior efficacy and overall survival data in [patients with] relapsed ES-SCLC. Now it is becoming more standard to use tarlatamab in the relapsed second-line [setting] and beyond.

Reference

FDA grants accelerated approval to tarlatamab-dlle for extensive stage small cell lung cancer. News release. FDA. May 16, 2024. Accessed September 23, 2025. https://tinyurl.com/48k34rw5